【摘要】 测定R-hap在健康Wistar大鼠体内的组织分布,排泄及药动学参数。R-hap采用IODO-GEN标记,测定单次推注给药后¹²⁵I-R-hap的组织分布,尿、粪及胆汁的排泄情况。¹²⁵I-R-hap药动学参数也是在单次推注给药后测定。R-hap在体内广泛分布,在大部分器官中快速消除。其中肾的含量最高,脂肪的含量最低。累计排泄率为71.81%±2.15%（48小时）及94.71%±1.50%（120小时）。经尿排泄为主要的排泄途径,给药后120小时,尿及粪的累计排泄率分别为80.64%±1.47%,14.07%±0.95%。平均给药时曲线下面积为（8818.4±576.1）Bq/h/mL。R-hap的组织分布,排泄及药动学参数的结果为未来的临床试验设计提供了参考依据。更多还原

【Abstract】 The purpose of this study is to characterize the tissue distribution,excretion and pharmacokinetics profiles of R-hap in healthy Wistar rats.R-hap was radiolabeled by the IODO-GEN method.Tissue distribution and urinary,fecal and biliary excre- tion patterns of ¹²⁵I-R-hap were investigated following a single i.v.bolus injection.Pharmacokinetics properties of ¹²⁵I-R-hap were also examined after a single i.v.bolus injection.The trichloroacetic acid（TCA）precipitated radioactivity was widely dis- tributed and rapidly diminished in most tissues.Kidney contained the highest radioactivity among all organs and the distribution of ¹²⁵I-R-hap to fat was minimal,The cumulative excretion of ¹²⁵1-R-hap reached 71.81%±2.15% of the administered radioactivity at 48 h and 94.71%±1.50% at 120 h.Urinary excretion was the dominant route of elimination following i.v.administration,as 80.64%±1.47% and 14.07%±0.95% of administered radioactivity were recovered in urine and feces,respectively,in intact rats over 120 h.The mean areas under the plasma concentration-time curve was （8818.4±576.1） Bq/h/mL.The results of tissue dis- tribution,excretion and pharmacokinetics of R-hap in rats provided biopharmaceutical basis for the design of future clinical trials.更多还原